Umbilical cord mesenchymal stem cells suppress B-cell proliferation and differentiation

Che, Nan; Li, Xia; Zhou, Shiliang; Li, Rui; Shi, Dongyan; Lu, Liwei; Sun, Lingyun

doi:10.1016/j.cellimm.2012.02.004

Cited by 71 publications

(68 citation statements)

References 48 publications

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“…And our results kept consistent with the studies which demonstrated MSC [21] and PGE2 [33] shifting the balance towards a T helper type 2 response and humoral immunity. However, our present data were in contrast with a previous report describing MSC-mediated inhibition of proliferation and differentiation into immunoglobulin secretion cells of human peripheral B cells by Anna Corcione [42] and other teams [43][44][45][46]. And Nan Che also found human UC-MSC suppressed mice spleen B-cell proliferation and differentiation.…”

Section: Discussioncontrasting

confidence: 99%

Mesenchymal Stem Cells Support Proliferation and Terminal Differentiation of B Cells

Zhou

Han

et al. 2012

Cell Physiol Biochem

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Background: Mesenchymal stem cells (MSC) play important roles in modulating the activities of T lymphocytes, dendritic cells and natural killer cells. These immunoregulatory properties of MSC suggest their therapeutic potential in autoimmune diseases. However, the effects of MSC on B cells are still poorly understood. The present study was designed to investigate the interaction between MSC and B cells both in vitro and in vivo, and to determine the possible mechanism of action. Design and Method: The effect of human umbilical cord mesenchymal stem cells (UC-MSC) on proliferation and differentiation of B-cells were characterized in vitro, and we also tested the immunoregulatory properties of mouse bone marrow MSC (BM-MSC) on T cell dependent and independent antibody production in vivo in mice. Results: Treatment with human UC-MSC resulted in an increase of proliferation, differentiation of B cells into plasma cells and production of antibodies in vitro. Mouse BM-MSC significantly enhanced T cell dependent and independent antibodies production in vivo in mice. PGE2 partially mediated the immunosuppressive activity of human UC-MSC but IL-6 did not regulate this activity. Conclusion: MSC promote proliferation and differentiation of B cells in vitro and in vivo partially through PGE2 but not IL-6.

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Section: Discussioncontrasting

confidence: 99%

Mesenchymal Stem Cells Support Proliferation and Terminal Differentiation of B Cells

Zhou

Han

et al. 2012

Cell Physiol Biochem

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“…It is generally believed up to now that MSCs from healthy human and normal mice can inhibit B cell proliferation, differentiation, and Ab secretion in vitro, although the published data are not unanimous, which might be because of different experimental systems and conditions (7,8,36,37). Our results are in line with the data that NMSCs are inhibitory for B cells in a dose-dependent way and mediated by soluble factors.…”

Section: Discussionsupporting

confidence: 88%

“…Data were acquired on a FACSCalibur flow cytometer using the Cell Quest software program. A minimum of 10,000 events/tube was collected for analysis (8).…”

Section: Differentiation Assaymentioning

confidence: 99%

“…However, for mature B cells, human bone marrow MSCs (BMMSCs) have been reported to inhibit B cell proliferation, differentiation, and chemotaxis (7). We have previously shown that normal human umbilical cord MSCs markedly suppressed the proliferation and differentiation of mouse splenic B cells as demonstrated by the decreased number of CD138 + cells and reduced levels of IgM and IgG (8). However, the underlying mechanisms by which MSCs suppress B cell function remain largely unknown.…”

mentioning

confidence: 99%

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Impaired B Cell Inhibition by Lupus Bone Marrow Mesenchymal Stem Cells Is Caused by Reduced CCL2 Expression

Che

Zhang

et al. 2014

The Journal of Immunology

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Mesenchymal stem cells (MSC) from healthy human and normal mice can inhibit normal B cell proliferation, differentiation, and Ab secretion in vitro. However, it remains unknown whether MSC from lupus-like mice and patients with systemic lupus erythematosus (SLE) exhibit the same immunoregulatory activity as normal MSC for B cell inhibition and, if not, what the underlying molecular mechanism would be. In this study, we showed that bone marrow-derived MSCs from lupus-like mice and SLE patients had an impairment in suppressing normal B cell proliferation and differentiation, which was caused by the reduction of CCL2 levels. Knockdown of CCL2 in normal MSC damaged their suppressive capacity for B cells. Conversely, overexpression of CCL2 in lupus MSCs restored their immunoregulatory ability for B cells in vitro and ameliorated the pathology of lupus nephritis and serological changes in MRL/lpr mice in vivo. Mechanistically, MSC-mediated B cell inhibition was dependent on matrix metalloproteinase proteolytic processing of CCL2. These findings reveal a novel function of CCL2 in B cell regulation by MSCs and suggest that CCL2 manipulation on MSCs may serve as a potential pathway for developing the more effective MSC-based therapy in autoimmune diseases associated with B cell activation, such as SLE.

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“…UC-MSCs have great immunomodulation capacity [9]; they act on the innate immunity by inhibiting the maturation and the activation of dendritic cells [10], the activation of the CD56 dim NK subpopulation, and NK cytotoxicity [11]. Moreover, UCMSCs have an influence on adaptive immunity by blocking T cell proliferation [9,10] and modulating B cell proliferation and differentiation [12,13]. Thus, UC-MSCs have become an appealing cell source for treatment of diseases where inflammation plays a crucial role such as graftversus-host disease [14] (www.clinicaltrials.gov; Identifier: NCT02032446).…”

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confidence: 99%

Transplanted Umbilical Cord Mesenchymal Stem Cells Modify the In Vivo Microenvironment Enhancing Angiogenesis and Leading to Bone Regeneration

Todeschi

Backly

Capelli

et al. 2015

Stem Cells and Development

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Umbilical cord mesenchymal stem cells (UC-MSCs) show properties similar to bone marrow mesenchymal stem cells (BM-MSCs), although controversial data exist regarding their osteogenic potential. We prepared clinical-grade UC-MSCs from Wharton's Jelly and we investigated if UC-MSCs could be used as substitutes for BM-MSCs in muscoloskeletal regeneration as a more readily available and functional source of MSCs. UCMSCs were loaded onto scaffolds and implanted subcutaneously (ectopically) and in critical-sized calvarial defects (orthotopically) in mice. For live cell-tracking experiments, UC-MSCs were first transduced with the luciferase gene. Angiogenic properties of UC-MSCs were tested using the mouse metatarsal angiogenesis assay. Cell secretomes were screened for the presence of various cytokines using an array assay. Analysis of implanted scaffolds showed that UC-MSCs, contrary to BM-MSCs, remained detectable in the implants for 3 weeks at most and did not induce bone formation in an ectopic location. Instead, they induced a significant increase of blood vessel ingrowth. In agreement with these observations, UC-MSC-conditioned medium presented a distinct and stronger proinflammatory/chemotactic cytokine profile than BM-MSCs and a significantly enhanced angiogenic activity. When UC-MSCs were orthotopically transplanted in a calvarial defect, they promoted increased bone formation as well as BM-MSCs. However, at variance with BM-MSCs, the new bone was deposited through the activity of stimulated host cells, highlighting the importance of the microenvironment on determining cell commitment and response. Therefore, we propose, as therapy for bone lesions, the use of allogeneic UC-MSCs by not depositing bone matrix directly, but acting through the activation of endogenous repair mechanisms.

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Umbilical cord mesenchymal stem cells suppress B-cell proliferation and differentiation

Cited by 71 publications

References 48 publications

Mesenchymal Stem Cells Support Proliferation and Terminal Differentiation of B Cells

Mesenchymal Stem Cells Support Proliferation and Terminal Differentiation of B Cells

Impaired B Cell Inhibition by Lupus Bone Marrow Mesenchymal Stem Cells Is Caused by Reduced CCL2 Expression

Transplanted Umbilical Cord Mesenchymal Stem Cells Modify the In Vivo Microenvironment Enhancing Angiogenesis and Leading to Bone Regeneration

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